Epilepsy is a common chronic neurological disorder that is characterized by recurrent unprovoked seizures. These seizures are transient signs or symptoms due to abnormal, excessive or synchronous neuronal activity in the brain. About 50 million people worldwide have epilepsy at any one time. Epilepsy is usually controlled, but not cured, with medication. While medication or surgery provide seizure control in most cases, over 30% of people with epilepsy do not have seizure control even with the best available medications.
The first line of treatment for epilepsy is anticonvulsant medication. Some people with epilepsy will experience a complete remission when treated with an anticonvulsant medication. If this does not occur, the dose of medication may be increased, or another medication may be added to the first. The general strategy is to increase the medication dose until either the seizures are controlled, or until dose-limiting side effects appear; at which point the medication dose is reduced to the highest amount that does not produce undesirable side effects. If a person's epilepsy cannot be brought under control after adequate trials of two or three different medications, that person's epilepsy is generally classified as “medically refractory.”
Surgical treatment can be an option for epilepsy when an underlying brain abnormality, such as a benign tumor or an area of scar tissue (e.g. hippocampal sclerosis) can be identified. The abnormality must be removable by a neurosurgeon. Surgery is usually only offered to patients when their epilepsy has not been controlled by adequate attempts with multiple medications. The most common form of resective surgical treatment for epilepsy is to remove the front part of either the right or left temporal lobe.
For those with medically refractory epilepsy that are not candidates for surgery or for whom surgery has not worked, few treatment options exist. One option is the ketogenic diet, a high-fat, low-carbohydrate, and adequate protein diet. While the ketogenic diet is effective in children with medically refractory epilepsy, its adverse effects and the parental effort involved in implementing and maintaining the diet limit its use.
Another treatment option is the use of neuropeptides that have anticonvulsant effects. Both neuropeptide Y and galanin have anticonvulsant effects in seizure animal models. However, the potential of neuropeptides as anticonvulsants remains unexploited except for adrenocorticotropic hormone, which is an accepted treatment for some childhood epilepsies. The clinical utility of neuropeptides such as neuropeptide Y and galanin is limited because they are not suited for peripheral administration since they do not cross the blood-brain barrier.
Due to the adverse effects and uncertainty associated with the few treatment options for those with medically refractory epilepsy, there is a need for new treatment options. Further, an easily administrated, highly effective anticonvulsant medication that crosses the blood-brain barrier is highly desired.